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Reviewed, UniProtKB/Swiss-Prot Q9Y672 (ALG6_HUMAN)

Last modified June 16, 2009. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
    EC=2.4.1.-
Alternative name(s):
    Dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase
    Asparagine-linked glycosylation protein 6
Gene names
Name: ALG6
ORF Names: My046
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man9GlcNAc(2)-PP-Dol.

Pathway

Protein modification; protein glycosylation.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Potential.

Involvement in disease

Defects in ALG6 are the cause of congenital disorder of glycosylation type 1C (CDG1C) [MIM:603147]; also known as carbohydrate-deficient glycoprotein syndrome type V. CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1C patients have muscular hypotonia, show a delayed statomotor development and are mentally retarded. CDG1C is biochemically characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2 in the endoplasmic reticulum. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.12

Sequence similarities

Belongs to the ALG6/ALG8 glucosyltransferase family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DiseaseCongenital disorder of glycosylation
Disease mutation
   DomainTransmembrane
   Molecular functionGlycosyltransferase
Transferase
Gene Ontology (GO)
   Biological processprotein amino acid N-linked glycosylation Ref.1 Ref.5 Ref.7

Inferred from genetic interaction. Source: UniProtKB

   Cellular componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionglucosyltransferase activity Ref.1

Inferred from direct assay. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 507507Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
PRO_0000174156

Regions

Transmembrane4 – 2421 Potential
Transmembrane115 – 13521 Potential
Transmembrane144 – 16421 Potential
Transmembrane173 – 19321 Potential
Transmembrane227 – 24721 Potential
Transmembrane298 – 31821 Potential
Transmembrane324 – 34421 Potential
Transmembrane362 – 38221 Potential
Transmembrane388 – 40821 Potential
Transmembrane438 – 45821 Potential
Transmembrane473 – 49321 Potential

Natural variations

Natural variant1311Y → H in CDG1C. dbSNP rs35383149.
VAR_022511
Natural variant1701S → I in CDG1C. Ref.9
VAR_022512
Natural variant2261K → N: dbSNP rs35604168.
VAR_055493
Natural variant2271G → E in CDG1C. Ref.10
VAR_022513
Natural variant2991Missing in CDG1C. Ref.7
VAR_013441
Natural variant3041F → S Common polymorphism; reduces the ability to rescue defective glycosylation of an alg6-deficient strain of S. cerevisiae during rapid growth; may exacerbate the clinical severity of patients with CDG1A. dbSNP rs4630153. Ref.6 Ref.7 Ref.3 Ref.8 Ref.11
VAR_013442
Natural variant3081S → R in CDG1C. Ref.5
VAR_022514
Natural variant3331A → V in CDG1C. Ref.1 Ref.5 Ref.6
VAR_013443
Natural variant4441Missing in CDG1C. Ref.9
VAR_022515
Natural variant4781S → P in CDG1C. Ref.6
VAR_013444

Experimental info

Sequence conflict1111F → L in AAG43163. Ref.2
Sequence conflict3741T → P in AAG43163. Ref.2
Sequence conflict3941T → P in AAG43163. Ref.2
Sequence conflict4571T → A in AAG43163. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y672-1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 6558E0A318597D03

FASTA50758,181
        10         20         30         40         50         60 
MEKWYLMTVV VLIGLTVRWT VSLNSYSGAG KPPMFGDYEA QRHWQEITFN LPVKQWYFNS 

        70         80         90        100        110        120 
SDNNLQYWGL DYPPLTAYHS LLCAYVAKFI NPDWIALHTS RGYESQAHKL FMRTTVLIAD 

       130        140        150        160        170        180 
LLIYIPAVVL YCCCLKEIST KKKIANALCI LLYPGLILID YGHFQYNSVS LGFALWGVLG 

       190        200        210        220        230        240 
ISCDCDLLGS LAFCLAINYK QMELYHALPF FCFLLGKCFK KGLKGKGFVL LVKLACIVVA 

       250        260        270        280        290        300 
SFVLCWLPFF TEREQTLQVL RRLFPVDRGL FEDKVANIWC SFNVFLKIKD ILPRHIQLIM 

       310        320        330        340        350        360 
SFCFTFLSLL PACIKLILQP SSKGFKFTLV SCALSFFLFS FQVHEKSILL VSLPVCLVLS 

       370        380        390        400        410        420 
EIPFMSTWFL LVSTFSMLPL LLKDELLMPS VVTTMAFFIA CVTSFSIFEK TSEEELQLKS 

       430        440        450        460        470        480 
FSISVRKYLP CFTFLSRIIQ YLFLISVITM VLLTLMTVTL DPPQKLPDLF SVLVCFVSCL 

       490        500 
NFLFFLVYFN IIIMWDSKSG RNQKKIS 

« Hide

References

« Hide 'large scale' references
[1]"A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic."
Imbach T., Burda P., Kuhnert P., Wevers R.A., Aebi M., Berger E.G., Hennet T.
Proc. Natl. Acad. Sci. U.S.A. 96:6982-6987(1999) [PubMed: 10359825] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CDG1C VAL-333.
[2]Mao Y.M., Xie Y., Zheng Z.H.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal brain.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-304.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]"Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation."
Westphal V., Murch S., Kim S., Srikrishna G., Winchester B., Day R., Freeze H.H.
Am. J. Pathol. 157:1917-1925(2000) [PubMed: 11106564] [Abstract]
Cited for: VARIANTS CDG1C HIS-131; ARG-308 AND VAL-333.
[6]"Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic."
Imbach T., Gruenewald S., Schenk B., Burda P., Schollen E., Wevers R.A., Jaeken J., de Klerk J.B.C., Berger E.G., Matthijs G., Aebi M., Hennet T.
Hum. Genet. 106:538-545(2000) [PubMed: 10914684] [Abstract]
Cited for: VARIANTS CDG1C VAL-333 AND PRO-478, VARIANT SER-304.
[7]"Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation Ic."
Westphal V., Schottstaedt C., Marquardt T., Freeze H.H.
Mol. Genet. Metab. 70:219-223(2000) [PubMed: 10924277] [Abstract]
Cited for: VARIANT CDG1C ILE-299 DEL, VARIANT SER-304.
[8]"The T911C (F304S) substitution in the human ALG6 gene is a common polymorphism and not a causal mutation of CDG-Ic."
Vuillaumier-Barrot S., Le Bizec C., Durand G., Seta N.
J. Hum. Genet. 46:547-548(2001) [PubMed: 11558905] [Abstract]
Cited for: VARIANT SER-304.
[9]"A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases."
de Lonlay P., Seta N., Barrot S., Chabrol B., Drouin V., Gabriel B.M., Journel H., Kretz M., Laurent J., Le Merrer M., Leroy A., Pedespan D., Sarda P., Villeneuve N., Schmitz J., van Schaftingen E., Matthijs G., Jaeken J. expand/collapse author list , Koerner C., Munnich A., Saudubray J.-M., Cormier-Daire V.
J. Med. Genet. 38:14-19(2001) [PubMed: 11134235] [Abstract]
Cited for: VARIANTS CDG1C ILE-170 AND LEU-444 DEL.
[10]"DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG)."
Schollen E., Martens K., Geuzens E., Matthijs G.
Eur. J. Hum. Genet. 10:643-648(2002) [PubMed: 12357336] [Abstract]
Cited for: VARIANT CDG1C GLU-227.
[11]"A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency."
Westphal V., Kjaergaard S., Schollen E., Martens K., Gruenewald S., Schwartz M., Matthijs G., Freeze H.H.
Hum. Mol. Genet. 11:599-604(2002) [PubMed: 11875054] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT SER-304.
[12]"Identification of a frequent variant in ALG6, the cause of congenital disorder of glycosylation-Ic."
Westphal V., Xiao M., Kwok P.-Y., Freeze H.H.
Hum. Mutat. 22:420-421(2003) [PubMed: 14517965] [Abstract]
Cited for: VARIANT CDG1C HIS-131.
+Additional computationally mapped references.

Web resources

GeneReviews
GGDB

GlycoGene database

Cross-references

Sequence databases

AF102851 mRNA. Translation: AAD41466.1.
AF063604 mRNA. Translation: AAG43163.1.
AL592218, AL049636 Genomic DNA. Translation: CAI18961.1.
AL049636, AL592218 Genomic DNA. Translation: CAI22829.1.
BC001253 mRNA. Translation: AAH01253.1.
IPIIPI00797222.
RefSeqNP_037471.2.
UniGeneHs.258501

3D structure databases

ModBaseSearch...

Protein family/group databases

CAZyGT57. Glycosyltransferase Family 57.

Proteomic databases

PRIDEQ9Y672.

Genome annotation databases

EnsemblENSG00000088035. Homo sapiens. [Contig view]
GeneID29929.
KEGGhsa:29929.

Organism-specific databases

GeneCardsGC01P063605.
H-InvDBHIX0000661.
HGNCHGNC:23157. ALG6.
MIM603147. phenotype.
604566. gene.
Orphanet137. CDG syndrome.
79320. CDG syndrome, type Ic.
PharmGKBPA134925619.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9Y672.

Gene expression databases

ArrayExpressQ9Y672.
BgeeQ9Y672.
CleanExHS_ALG6.
GermOnlineENSG00000088035. Homo sapiens.

Family and domain databases

InterProIPR004856. Glycosyltransferase_ALG6/ALG8.
[Graphical view]
PANTHERPTHR12413. Alg6_Alg8. 1 hit.
PfamPF03155. Alg6_Alg8. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio52559.
SOURCESearch...

Entry information

Entry nameALG6_HUMAN
AccessionPrimary (citable) accession number: Q9Y672
Secondary accession number(s): Q5SXR9, Q9H3I0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: November 1, 1999
Last modified: June 16, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents